crestor presentation
DESCRIPTION
Crestor PPTTRANSCRIPT
Assurance of
Cardiovascular Risk Reduction comes from broad Clinical Experience
GALAXY Presentation - suggested execution 1
Is Lower Better? Relationship between LDL-C and CV Event Rate
Rosenson RS. Exp Opin Emerg Drugs 2004;9(2):269-279, LaRosa JC et al. N Engl J Med 2005;352:1425-1435.
LDL-C achieved mg/dL (mmol/L)
WOSCOPS – Pl
AFCAPS - Pl
ASCOT - PlAFCAPS - Rx WOSCOPS - Rx
ASCOT - Rx
4S - Rx
HPS - Pl
LIPID - Rx
4S - Pl
CARE - Rx
LIPID - Pl
CARE - Pl
HPS - Rx
0
5
10
15
20
25
30
40(1.0)
60(1.6)
80(2.1)
100(2.6)
120(3.1)
140(3.6)
160(4.1)
180(4.7)
Even
t ra
te (
%)
6
Secondary Prevention
Primary Prevention
Rx - Statin therapyPl – PlaceboPra – pravastatinAtv - atorvastatin
200(5.2)
PROVE-IT - Pra
PROVE-IT – Atv
TNT – Atv10
TNT – Atv80
INTRO
STELLAR
PEPI
METEOR
ASTEROID
JUPITER
Half of patients on lipid lowering therapy are not reaching goal2
EUROASPIRE II which reported in 2001 confirmed that half of treated CHD patients were still not at European total cholesterol goal
Patients on lipid lowering therapy at European goal
50%25% 75% 100%
EUROASPIRE II: achievement of total cholesterol treatment goal
51%
Lipid management assessed in 5556 patients with CHD at least 6 months after discharge who qualify for treatment
EUROASPIRE II. Eur Heart J 2001;22:554–572
NCEP ATP III: LDL-C Goals (2004 proposed modifications)
*Therapeutic option
70 mg/dL =1.8 mmol/L; 100 mg/dL = 2.6 mmol/L; 130 mg/dL = 3.4 mmol/L; 160 mg/dL = 4.1 mmol/L
High Risk
CHD or CHD risk equivalents
(10-yr risk >20%)
100 -
160 -
130 -
190 -
Lower Risk
< 2 risk factors
Moderately High Risk
≥ 2 risk factors
(10-yr risk 10-20%)
goal
160mg/dL
goal
130mg/dL
70 -
goal
100 mg/dL
or optional
70 mg/dL*
Moderate Risk
≥ 2 risk factors
(10-yr risk <10%)
goal
130 mg/dL
or optional
100 mg/dL*
Grundy SM et al. Circulation 2004;110:227-239.
Existing LDL-C goals
Proposed LDL-C goals
LD
L-C
LEV
EL
Relationship Between Changes in LDL-C and HDL-C Levels and CHD Risk
Third Report of the NCEP Expert Panel. NIH Publication No. 01-3670 2001. http://hin.nhlbi.nih.gov/ncep_slds/menu.htm
1% decreasein LDL-C reduces
CHD risk by1%
1% increasein HDL-C reduces
CHD risk by1-3%
INTRO
STELLAR
PEPI
METEOR
ASTEROID
JUPITER
Rosuvastatin Atorvastatin Simvastatin
Pravastatin
*p<0.002 vs atorvastatin 10 mg; simvastatin 10, 20, 40 mg; pravastatin 10, 20, 40 mg†p<0.002 vs atorvastatin 20, 40 mg; simvastatin 20, 40, 80 mg; pravastatin 20, 40 mg‡p<0.002 vs atorvastatin 40 mg; simvastatin 40, 80 mg; pravastatin 40 mg
*
X
X
X
–60
–50
–40
–30
–20
–10
0
Dose, mg (log scale)10 20 40 80
X
X
n=648
n=473
n=634
n=485
†‡
Ch
an
ge in
LD
L-C
fro
m
baselin
e (
%)
Rosuvastatin versus Comparators:LDL-C Efficacy Across the Dose Range
The STELLAR Study
INTRO
STELLAR
PEPI
METEOR
ASTEROID
JUPITER
Jones PH et al. Am J Cardiol 2003;92:152–160
Rosuvastatin versus other statins - change in HDL-C
The STELLAR Study
*p<0.002 vs pravastatin 10 mg†p<0.002 vs atorvastatin 20, 40, 80 mg; simvastatin 40 mg; pravastatin 20, 40 mg‡p<0.002 vs atorvastatin 40, 80 mg; simvastatin 40 mg; pravastatin 40 mgObserved data in ITT population
10 20 40
3.2
4.4
5.6
10 20 40 80 10 20 40 0
2
4
6
8
10
12
5.74.8
4.4
2.1
*7.7
†9.5
‡9.6
10 20 40 80
5.3
6.0
5.2
6.8
Dose (mg)
RosuvastatinAtorvastatin
PravastatinSimvastatin
Ch
an
ge in
HD
L-C
fro
m
baselin
e (
%)
INTRO
STELLAR
PEPI
METEOR
ASTEROID
JUPITER
Jones PH et al. Am J Cardiol 2003;92:152–160
CV Risk Reduction – Head-to- head comparison In ‘’Real Life’’All statin users between January 2000 and September
2005
rosuvastatinN = 8,088
atorvastatinN = 25,777
simvastatinN = 27,752
pravastatinN = 14,530
Exclude: •Established statin users (prior statin use in last 12 months)
•patients with CV event in previous 12 months•patients with <12 months history in PHARMO
•cerivastatin and fluvastatin users* •Use of >1 statin simultaneously
•patients under 18
N = 76,147 Followed until first CV event or cessation of initial statin use or loss to follow-up in
the database
* Cerivastatin was withdrawn from the market in 2002. There were too few fluvastatin users for any meaningful analyses
Heintjes et al, Current Medical Opinion and Research, July 2008 PEPI
INTRO
STELLAR
PEPI
METEOR
ASTEROID
JUPITER
Retrospective observational cohort study
Primary outcome: Cardiovascular (CV) Hospitalisations
Fatal and non-fatal ischaemic heart disease, myocardial infarction (MI), fatal and non-fatal stroke, coronary and carotid revascularisation
Secondary outcome
Hospitalisations for MI
Hazard ratios¶ with 95% confidence intervals calculated
Adjusted for patient characteristics, co-morbidities and co-medications
*I.e. CV events counted whilst on original statin
¶ The ‘hazard ratio’ was the ratio of the incidence of CV events on rosuvastatin versus that on other statins
CV Risk Reduction – Head-to- head comparison In ‘’Real Life’’
PEPI
INTRO
STELLAR
PEPI
METEOR
ASTEROID
JUPITER
Heintjes et al, Current Medical Opinion and Research, July 2008
Primary OutcomeRates of CV events were 28% lower on CRESTOR compared with other statins
0.4
0.6
0.8
1.0
1.2
1.4
CRESTOR vs. other statins
CRESTOR (10.8 mg) vs.
ATV (17.3 mg)
RSV better RSV worse
CRESTOR (10.8 mg) vs.
SMV (22.1 mg)
CRESTOR (10.8 mg) vs.
PRV (33.8 mg)
* * A 95% CI that does not exceed 1 indicates a statistically significant hazard ratio A 95% CI that does not exceed 1 indicates a statistically significant hazard ratio
0.72 (0.56-0.94) *
0.83 (0.63-1.10) NS
0.71 (0.54-0.94) *
0.60 (0.45-0.80) *
Hazard ratios of CV were adjused for age, gender, nitrates, classic antihypertensives and diabetes
Adjusted hazard ratio of CV hospitalisations (95% CI)
28%
17%
29%
40%
Reduction in CV events
PEPI
INTRO
STELLAR
PEPI
METEOR
ASTEROID
JUPITER
Heintjes et al, Current Medical Opinion and Research, July 2008
US StudyPatient selection
All statin users between August 2003 and December 2005
rosuvastatinN = 45,510
atorvastatinN = 196,523
simvastatinN = 73,884
pravastatinN = 25,055
Exclude: •established statin users (prior statin use in last 12
months)•serious non-CV disease or immunosuppression
•with <12 months history in database•patients under 18
N = 395,056Followed until: first CV event, switch to another statin
therapy or switch/add another lipid-lowering therapy or 90 days after end of statin supply or loss to follow-up in the
database
lovastatinN = 45,483
fluvastatinN = 8,584
INTRO
STELLAR
PEPI
METEOR
ASTEROID
JUPITER
Heintjes et al, Current Medical Opinion and Research, July 2008
US Study Results: Reduction in CV events
>=90 days
>=180 days
>=270 days
0.95 (0.84-1.08)
0.88 (0.74-1.05)
0.76 (0.59-0.97) ‡
RSV better Other statins† better0.6
0.8
1.0
1.2
0.97 (0.86-1.08)
0.91 (0.78-1.06)
0.80 (0.64-1.00) ‡
MPR>0.8
MPR>0.8
MPR>0.8
‡‡ A 95% CI that does not exceed 1 indicates a statistically significant hazard ratio A 95% CI that does not exceed 1 indicates a statistically significant hazard ratio
Adjusted* hazard ratio of CV events (95% CI)
20%Reduction in CV events
In patients with higher compliance¶ and longer exposure times, a trend of a higher decreased CV event rate with RSV as compared to other statins was found
INTRO
STELLAR
PEPI
METEOR
ASTEROID
JUPITER
N = 395,056
Heintjes et al, Current Medical Opinion and Research, July 2008
What about efficacy in atherosclerosis?
Which is the Most Effective Statin in Regression of athersclerosis?
INTRO
STELLAR
PEPI
METEOR
ASTEROID
JUPITER
ENHANCE METEOR
Patients High-risk FH (n=720) Lower risk asymptomatic subjects at low risk of CHD (n=984)
LDL-C Baseline LDL-C 319mg/dL; 8.3mmol/L
Mean baseline LDL-C 155mg/dL; 4mmol/L
CIMT analysed
Mean change from baseline in CIMT using composite measures from the right + left far wall CCA, carotid bulb and ICA
6 sites – far wall only
Max CIMT, based on 12 carotid artery segments (near & far wall of the right and left CCA, carotid bulb and ICA)
12 sites – near and far walls
Status Completed April ‘06, press release 14 Jan 08. Likely to jeopardise presentation of results at ACC Mar ’08 (23 months later).
Completed May ’06, data at ACC Mar ’07 (10 months later)
Results No statistical difference in mean CIMT (primary endpoint), or in individual components of primary endpoint, including CCA.
CRESTOR 40 mg slowed the rate of progression of maximum CIMT vs placebo ….and with significant regression of CIMT in the CCA
ENHANCE vs METEOR
INTRO
STELLAR
PEPI
METEOR
ASTEROID
JUPITER
Kasteline J et al, NEJM April, 2008 Crouse J et al, JAMA, 2007
Time (years)
-0.01
+0.01
0.00
+0.02
21
+0.03
Pro
gre
ssio
n
Regre
ssio
n
P=NS(CRESTOR vs. zero slope
Placebo+0.0131 mm/yr
(n=252)
Rosuvastatin 40 mg-0.0014 mm/yr
(n=624)
P<0.001 (CRESTOR vs. placebo)
Placebo; Change in CIMT (95% CI)
Rosuvastatin 40 mg; Change in CIMT (95% CI)
METEOR primary endpoint:Rate of change of maximum IMT at 12 carotid sites Rosuvastatin vs placebo
Crouse JR III, et al. JAMA 2007;297 (12):1344–1353
INTRO
STELLAR
PEPI
METEOR
ASTEROID
JUPITER
48% reduction LDL-C
8% Increase HDL-C
ENHANCE results
Time (years)-0.01
+0.01
0.00
+0.02
+0.03
Pri
mary
End
poin
tC
hang
e in m
ean IM
T a
t 6 c
aro
tid s
ites
(mm
)
SMV 80 + EZE +0.0111 mm
p=0.29 (ns)
SMV 80 +0.0058 mm
• 720 patients with familial hypercholesteraemia• 1° endpoint: Absolute change in mean cIMT • Measured at 6 carotid sites• Most patients established statin users
21
Ezetimibe/simvastatin 10/80mg showed no significant difference to simvastatin 80mg on the primary endpoint (mean CIMT), on any component of the primary endpoint, or on any of the secondary
imaging endpointsINTRO
STELLAR
PEPI
METEOR
ASTEROID
JUPITER
Kasteline J et al, NEJM April, 2008
ENHANCE failed to meet its primary and secondary endpoints and showed that adding ezetimibe to simvastatin provides no benefit on the treatment of atherosclerosis
CRESTOR has the proven efficacy to lower LDL-C, raise HDL-C, and has been shown to slow the progression of atherosclerosis at any stage of the disease
CRESTOR significantly slowed the progression of atherosclerosis in the METEOR study (which employed very similar methodology to ENHANCE). These results were pivotal to achieving the unique atherosclerosis indication granted by US FDA
Summary : METEOR & ENHANCE Results
A Study To evaluate the Effect of
Rosuvastatin On Intravascular
ultrasound-Derived coronary
atheroma burden
Nissen S et al. JAMA 2006;295 (13):1556-1565;
Ballantyne C et al. Circulation 2008 DOI: 10.1161/CIRCULATIONAHA.108.773747.
ASTEROID used intravascular ultrasound (IVUS) and quantitative coronary angiography (QCA) to evaluate the effect
of rosuvastatin (CRESTOR™) on atherosclerotic disease in patients with coronary artery disease (CAD)
INTRO
STELLAR
PEPI
METEOR
ASTEROID
JUPITER
Lumenarea
EEM area
Atheroma area
Ultrasound Determination of Atheroma Area
Precise planimetry of EEM and lumen borderswith calculation of atheroma cross-sectional area
INTRO
STELLAR
PEPI
METEOR
ASTEROID
JUPITER
Example of regression of atherosclerosis with
rosuvastatin in ASTEROID, measured by IVUS
Images courtesy of Cleveland Clinic Intravascular Ultrasound Core Laboratory
Effects of Rosuvastatin on intravascular ultrasound (IVUS) - derived coronary artery atheroma burden The ASTEROID study
INTRO
STELLAR
PEPI
METEOR
ASTEROID
JUPITER
53% reduction LDL-C
14% Increase HDL-C
2
The relationship between mean LDL-C and change in percent atheroma volume (PAV) in IVUS studies†
Change in Percent
AtheromaVolume*
(%)
1 Nissen S et al. N Engl J Med 2006;354:1253-1263. 2 Tardif J et al. Circulation 2004;110:3372-3377. 3 Nissen S et al. JAMA 2006;295 (13):1556-1565 4 Nissen S et al. JAMA 2004;292: 2217–2225. 5 Nissen S et al. JAMA 2004; 291:1071–1080
-1
-0.5
0
0.5
1
1.5
50 60 70 80 90 100 110 120
A-Plus2 placebo
ACTIVATE1 placebo
CAMELOT4 placebo
REVERSAL5 pravastatin
REVERSAL5 atorvastatin
Mean LDL-C (mg/dL)
Progression
Regression
ASTEROID3 rosuvastatin
INTRO
STELLAR
PEPI
METEOR
ASTEROID
JUPITER
Change in Percent Diameter Stenosis vs On-Treatment LDL-C in QCA Trials
* ASTEROID - rosuvastatin; MAAS - simvastatin; CCAIT - lovastatin; MARS – lovastatin; LCAS - fluvastatin; PLAC I - pravastatin
Chang
e in %
Ste
nosi
s per
year
40 60 80 100 120 140 160 180
-1
-0.8
-0.6
-0.4
-0.2
0
0.2
0.4
0.6
0.8
1
1.2
1.4
MARS MAAS
PLAC ILCAS
PLAC ICCAIT
LCASMAAS
MARS
On-Treatment LDL-C (mg/dL)
CCAITPlacebo
Statin*
Progression
Regression
Nissen S et al. JAMA 2006;295 (13):1556-1565; Ballantyne C et al. Circulation 2008 DOI: 10.1161/CIRCULATIONAHA.108.773747.
INTRO
STELLAR
PEPI
METEOR
ASTEROID
JUPITER
ASTEROID3 rosuvastatin
Atherosclerosis is the underlying cause of heart disease - the World’s number one killer
Rosuvastatin is the only statin to show regression of coronary atherosclerosis in a major clinical study
In ASTEROID, two imaging modalities that measure different parameters and focus on different segments of the coronary arteries have demonstrated concordant improvements in both IVUS measurements of atheroma volume and angiographic measurements of lumen dimension consistent with regression of atherosclerosis with intensive rosuvastatin therapy
CRESTOR Clinical Perspective in Atherosclerosis
METEOR ASTEROID
DISEASE PROGRESSION OVER TIME
EARLY DISEASE
ESTABLISHED DISEASE
US FDA approval for atherosclerosis as an indication- Nov. 2007
INTRO
STELLAR
PEPI
METEOR
ASTEROID
JUPITER
CRESTOR - Withdrawals due to Adverse Events
Percentage of patients with an adverse event leading to withdrawal
0
2
4
6
8
rosuvastatin simvastatin pravastatin
Pati
en
ts (
%)
1
3
5
7
2.9%2.5% 2.5%
(n=3074) (n=1457) (n=1278)
3.2%
atorvastatin(n=2899)
10–40 mg10–80 mg10–80 mg10–40 mg
Brewer HB. Am J Cardiol 2003;92(Suppl):23K–29K Shepherd J et al. Am J Cardiol 2004;94:882-888
CRESTOR – Liver Effects ALT >3 × ULN: Frequency by LDL-C Reduction
0.0
0.5
1.0
1.5
2.0
2.5
3.0
20 30 40 50 60 70
LDL-C reduction (%)
Fluvastatin (20, 40, 80 mg)
Rosuvastatin (10, 20, 40 mg)
Lovastatin (20, 40, 80 mg)
Atorvastatin (10, 20, 40, 80 mg)
Simvastatin (40, 80 mg)
Occu
rren
ce o
f A
LT >
3
×ULN
(%
)
Persistent elevation is elevation to >3 x ULN on 2 successive occasions
Brewer HB. Am J Cardiol 2003;92(Suppl):23K–29K
CRESTOR - Muscle Effects CK >10 x ULN: Frequency by LDL-C Reduction
Brewer HB. Am J Cardiol 2003;92(Suppl):23K–29K
0.0
0.5
1.0
1.5
2.0
2.5
3.0
20 30 40 50 60 70
LDL-C reduction (%)
Occu
rren
ce o
f C
K >
10 ×
ULN
(%
) Cerivastatin (0.2, 0.3, 0.4, 0.8 mg)
Rosuvastatin (10, 20, 40 mg)
Pravastatin (20, 40 mg)
Atorvastatin (10, 20, 40, 80 mg)
Simvastatin (40, 80 mg)
Justification for the Use of statins in
Primary prevention: an Intervention
Trial Evaluating Rosuvastatin
CV Risk Reduction –CRESTOR Outcome Study
Objective: The primary objective of the JUPITER study is to investigate whether long-term treatment with rosuvastatin 20 mg decreases the rate of first major cardiovascular events compared with placebo in patients with low LDL-C but with increased risk as identified by elevated CRP levels
Ridker PM et al. Am J Cardiol 2007; 100: 1659–1664.
INTRO
STELLAR
PEPI
METEOR
ASTEROID
JUPITER
20% ReductionMortality
44% ReductionCV events
48% Reduction
Stroke
47% ReductionUnstable
angina
CV Risk Reduction –CRESTOR Outcome Study
INTRO
STELLAR
PEPI
METEOR
ASTEROID
JUPITER
47% ReductionCombined
CV risk
54% Reduction
Heart attack
Landmark Statin Trial - Highlights
Trial Year published
Population Treatment % LDL-C
RRR*
4S 1994 High cholesterol
CHD
S 20-40 mg -35% -34%
WOSCOPS 1995 High cholesterol
No CHD
P 40 mg -26% -31%
CARE 1996 Average cholesterol
CHD
P 40 mg -32% -24%
AFCAPS/ TexCAPS
1998 Average cholesterol, low HDL-C
No CHD
L 20-40 mg -25% -37%
HPS 2002 Average cholesterol
CHD or a CHD risk equivalent
S 40 mg -29% -24%
JUPITER 2008 Low to normal LDL-C R20 -50% -44%
*Relative risk of experiencing a major CV event
INTRO
STELLAR
PEPI
METEOR
ASTEROID
JUPITER
LipidsCRP
Tolerability
LipidsCRP
TolerabilityHbA1C
Placebo
run-in
1–6
2–4
30
413
Final3–4 y 6-monthly
Randomisation
LipidsCRP
Tolerability
Rosuvastatin 20 mg (n~7500)
Placebo (n~7500)
Lead-in/eligibility
No history of CAD
men ≥50 yrs
women ≥60 yrs
LDL-C <130 mg/dL
CRP ≥2.0 mg/L
CAD=coronary artery disease; LDL-C=low-density lipoprotein cholesterol; CRP=C-reactive protein; HbA 1c=glycated haemoglobin
CV Risk Reduction –CRESTOR Outcome Study
Ridker PM et al. Am J Cardiol 2007; 100: 1659–1664.
INTRO
STELLAR
PEPI
METEOR
ASTEROID
JUPITER
Randomised (n=17,802)
mmol/L mg/dL
Total cholesterol
4.79 185
LDL-C 2.79 108
HDL-C 1.27 49
nonHDL-c 3.47 134
Triglycerides 1.33 118
Glucose 5.2 94
hsCRP, mg/L 4.3
HbA1c, % 5.7Values expressed as median (interquartile range). For hsCRP, values are the mean of the screening and randomization visits.LDL-C=low-density lipoprotein cholesterol; HDL-C=high-density lipoprotein cholesterol; hsCRP=median high sensitivity C-reactive protein; HbA1c=glycosylated haemoglobin
Ridker PM et al. Am J Cardiol 2007; 100: 1659–1664.
Laboratory parameters at baseline
INTRO
STELLAR
PEPI
METEOR
ASTEROID
JUPITER
0
1
2
3
4
5
6
7
8
9
0 1 2 3 4 5Years
Placebo
Rosuvastatin 20 mg
JUPITER - Primary Endpoint
Perc
en
t of
pati
en
ts w
ith
pri
mary
en
dp
oin
t
Number at risk RSV 8901 8412 3893 1353 538 157 Placebo 8901 8353 3872 1333 531 174
Hazard Ratio 0.56 (95% CI 0.46-0.69)P<0.00001
NNT for 2y = 95 5y* = 25
44% Reduction
Time to first occurrence of a CV death, non-fatal stroke, non-fatalMI, unstable angina or arterial revascularization
INTRO
STELLAR
PEPI
METEOR
ASTEROID
JUPITER
JUPITER - Total Mortality
Death from any cause
0
1
2
3
4
5
6
7
0 1 2 3 4 5Years
Placebo
Rosuvastatin 20mg
Perc
en
t to
tal m
ort
ality
Number at risk RSV 8901 8787 4312 1602 676 227 Placebo 8901 8775 4319 1614 681 246
Hazard Ratio 0.80 (95% CI 0.67-0.97)p=0.02 20%
ReductionINTRO
STELLAR
PEPI
METEOR
ASTEROID
JUPITER
JUPITER - Primary Endpoint Components
Primary Endpoint 251 (1.36) 142 (0.77) 0.56 0.46-0.69 <0.001*
(Time to first occurrence of CV death, MI, stroke, unstable angina, arterial revascularisation)
Non-fatal MI 62 (0.33) 22 (0.12) 0.35 0.22-0.58 <0.001*
Fatal or non-fatal MI 68 (0.37) 31 (0.17) 0.46 0.30-0.70 0.0002
Non-fatal stroke 58 (0.31) 30 (0.16) 0.52 0.33-0.80 0.003Fatal or non-fatal stroke 64 (0.34) 33 (0.18) 0.52 0.34-0.79 0.002
Arterial Revascularization 131 (0.71) 71 (0.38) 0.54 0.41-0.72 <0.0001
Unstable angina† 27 (0.14) 16 (0.09) 0.59 0.32-1.10 0.09
CV death, stroke, MI 157 (0.85) 83 (0.45) 0.53 0.40-0.69 <0.001*
Revascularization or unstable angina 143 (0.77) 76 (0.41) 0.53 0.40-0.70 <0.001*
Placebo Rosuvastatin HR95% CI p-value
[n=8901] [n=8901]
n (rate**) n (rate**)
** Rates are per 100 person years; † Hospitalisation due to unstable angina; *Actual p-value was < 0.00001
INTRO
STELLAR
PEPI
METEOR
ASTEROID
JUPITER
Tolerability and safety data
Adverse Events, (%) Any serious adverse event 15.5 15.2 0.60Muscle weakness, stiffness, pain 15.4 16.0 0.34Myopathy 0.1 0.1 0.82Rhabdomyolysis 0.0 <0.1* ----Newly diagnosed cancer 3.5 3.4
0.51Death from cancer 0.7 0.4
0.02Gastrointestinal disorders 19.2 19.7
0.43Renal disorders 5.4 6.0
0.08Bleeding 3.1 2.9
0.45Hepatic disorders 2.1 2.4
0.13
Other events, (%)Newly diagnosed diabetes** 2.4 3.0
0.01Haemorrhagic stroke 0.1 0.1
0.44
Placebo Rosuvastatin p-value [n=8901] [n=8901]
*Occurred after trial completion; **physician reported newly diagnosed diabetes
INTRO
STELLAR
PEPI
METEOR
ASTEROID
JUPITER
Laboratory Safety Data
Laboratory Values, N (%) Serum creatinine‡ 10 (0.10) 16 (0.20) 0.24ALT > 3 x ULN# 17 (0.20) 23 (0.30) 0.34Glycosuria† 32 (0.40) 36 (0.50) 0.64
Laboratory Values, median values (IQR) GFR*, (mL/min/1.73m2) 66.6 (58.8-76.2) 66.8 (59.1-76.5)0.02% HbA1c** 5.8 (5.6-6.1) 5.9 (5.7-6.1)0.001Fasting plasma glucose**, (mg/dL) 98 (90-106) 98 (91-107) 0.12
Placebo Rosuvastatin p-value[n=8901] [n=8901]
GFR = Glomerular filtration rate, HbA1c = Haemoglobin A1c
# on consecutive visits, ‡ >100% increase from baseline, *at 12 months, **at 24 months, †>trace at 12 months
INTRO
STELLAR
PEPI
METEOR
ASTEROID
JUPITER
JUPITER – summary and perspectives
The JUPITER study included patients with low to normal LDL-C who were at increased CV risk as identified by elevated CRP levels and who did not require statin treatment based on current treatment guidelines
A 44% reduction in the primary endpoint of major cardiovascular events (composite of: CV death, MI, stroke, unstable angina, arterial revascularisation) was observed in patients who received rosuvastatin 20 mg compared with placebo (p< 0.00001)
A 20% reduction in total mortality was observed in patients who received rosuvastatin 20 mg compared with placebo (p=0.02), a unique finding for statins in a population without established CHD
In JUPITER, long-term treatment with rosuvastatin 20 mg was well tolerated in nearly 9000 study participants
There was no difference between treatment groups for muscle weakness, cancer, haematological disorders, gastrointestinal, hepatic or renal systems
The results from JUPITER highlight the importance of highly effective statin treatment for these patients with an increased risk of CV disease
INTRO
STELLAR
PEPI
METEOR
ASTEROID
JUPITER
Assurance of Cardiovascular Risk Reduction comes from broad Clinical Experience
Best in class
HDL-C increase, and LDL-C decrease
1
PEPI 2
Nearly 500,000 a million patients in real life, have shown CRESTOR is superior in CV risk reduction as compared to all statins
First statin to show..treating dyslipidemia with Crestor halts the progression of atherosclerosis in low risk patients leading to US FDA approval in atherosclerosis indication
3
4 out of 5 patients showed coronary plaque regression in patients with
established CHD
4
First positive outcome on CRESTOR – Study halted
because of unequivocal superiority in cardiovascular
morbidity and mortality
5
CRESTOR- Offers Comprehensive Lipid Management